Anti-PIGF Therapy in Medulloblastoma

Background:

Medulloblastoma is the most common childhood brain tumor. It arises in the cerebellum, the part of the brain that controls coordination and movement. The standard treatment regimen consists of surgery, followed by a combination of intensive radiation and chemotherapy. Radiation therapy of the central nervous system in children is associated with severe side effects, including impaired cognitive function, neuroendocrine dysfunctions and secondary cancers. Currently, there is no treatment for resistant or relapsing tumors.

Project Goal:

The group of Dr. Jain has recently discovered that placental growth factor (PlGF, an angiogenic protein) is aberrantly expressed in more than 90% of primary pediatric medulloblastomas, regardless of their genetic subtype (Snuderl et al., Cell 2013). Using novel specific antibodies, they have shown that PlGF blockade causes dramatic regression of primary tumors and metastatic spinal spread, which leads to significant increase in survival in orthotopic models of medulloblastoma. Based on these findings, the group is currently testing -- with grant support from Alex Lemonade Stand Foundation -- the efficacy of PIGF blockade combined with radiotherapy to determine if the use of PlGF induces radiosensitization and, therefore, allows to lower the radiation dose necessary to treat these patients.